Background technology
The use of most of low frequency EMF combines with the application of bone repair (repair) and healing (healing).Like this, the current orthopedic clinical of EMF waveform and EMF waveform is used and is comprised relative low frequency component and very low power is arranged, and causes the maximum field in every centimetre one microvolt (mv/cm) scope at the frequency place that is lower than 5KHz.Using the electrochemistry model of cell membrane to predict can to expect the linear physico-chemical process of scope of the EMF waveform patterns of biological effect, is to be the basis that is assumed to be of possible EMF target with cell membrane (particularly be combined in the cell membrane or on ion).Therefore, must confirm the scope of waveform parameter, for this waveform parameter, induction field can electrochemically be coupled at cell surface for example through using the kinetics that relies on voltage.The expansion of this linear model comprises Lorentz (Lorentz) power Consideration, and its magnetic component that has finally confirmed EMF can play an important role in the EMF treatment.This causes in very low frequency range from the AC of merging and the ion cyclotron resonance and the quantum model of DC magnetic field effect prediction interests.
Continuous sinusoidal wave pulse radiation frequency (PRF) signal that produces by the 27.12MHz that is used for the deep tissues healing is known in the prior art field of diathermy.The follow-up thing of the pulse of diathermy signal is delivered to can in the treatment of infectious disease, exciting the electromagnetic field of non-thermal biological effect at first.Subsequently, reported PRF treatment application, be used for reducing after the wound and the edema of postoperative pain and soft tissue, wound healing, burn treatment and neuranagenesis.The application of PRF of traumatic edema of being used to disappear is used in recent years more and more.In animal and clinical research, use the result of PRF to show so far, edema can moderately be reduced owing to such electromagnetic stimulation.
The present invention is based on biophysics and zooscopy, it exchanges effect to organizational structure sensitivity owing to induced voltage and correlated current with cell and cell.Whether the EMF signal that the mathematical analysis of at least one in use signal to noise ratio (snr) and the PSNR power signal-to-noise ratio (Power SNR), estimation are applied to target pathway structure (like cell, tissue, organ and molecule) is detectable on the thermal noise of ions bind position appearance.The dielectric characteristic of organizational structure is not considered in the EMF dosimetry of prior art, and on the contrary, prior art is utilized the characteristic of isolated cells.Through utilizing dielectric characteristic, the SNR that estimates in the target pathway structure through optimization can strengthen with the activity coupling (reactive coupling) of the electromagnetic waveforms that the Power SNR mathematical value disposes: at the reparation of people, animal and plant cell, organ, tissue and intramolecular various wounds (for example behind the surgical operation and the wound healing of wound), angiogenesis; The hemoperfusion that improves, vasodilation, vasoconstriction; Decrease in edema, enhanced neovascularization, bone repair; Tendon is repaired; Ligament repair, neomorph, and pain relief.Wound repair enhancement results comes from the blood flow of increase and adjusting and other enhanced biological effect process of angiogenesis and neovascularization.
Noinvasive PRF utilizes the sinusoidal wave impulse train of 27.12MHz in the nearest clinical use of radio frequency, the general width of showing 65 microseconds of each impulse train, and nearly 1700 sinusoidal period of every impulse train, and have different pulse crowd repetitive rate.
Broad spectral density bursts with electromagnetic waveforms of the frequency in the scope of one to 100 megahertz (MHz) is selectively used for people, animal and plant cell, organ, tissue and molecule; Every impulse train has 1 to 100; 000 pulse; And burst repetition rate is 0.01 to 10,000 hertz (Hz).The voltage amplitude envelope of each impulse train be at random, the function of irregular or other like variable, be used in pulse burst envelope, providing broad-spectrum density.Through the mathematical function of the signal of consideration in specific target pathway structure, come defined variable with thermal noise ratio and Power SNR.Waveform Design becomes to regulate living cells growth, state and reparation.The application-specific of these signals includes but not limited to: strengthen the treatment of organ, muscle, joint, skin and hair, behind the surgical operation with the wound healing of wound, angiogenesis, the hemoperfusion of improvement; Vasodilation, vasoconstriction, decrease in edema; Enhanced neovascularization, bone repair, tendon reparation; Ligament repair, neomorph, and pain relief.The application of electromagnetic waveforms can be used for strengthening the healing of various wounds.
According to embodiment of the present invention, the pulse burst envelope of higher spectral density can more effectively be coupled to the dielectric pathways that the physiology is correlated with, for example cell-membrane receptor, change with bonded ion of cellular enzymes and general transmembrane potential.Increased the quantity of the frequency component that is transferred to relevant cellular pathways according to embodiment of the present invention; The biophysics phenomenon in a big way that causes can be applicable to known healing mechanism becomes and can realize, comprises enhanced enzymatic activity, growth factor release and release of cytokines.Through increasing the impulse train persistent period; Use at random or the pulse burst envelope of the envelope of other high spectrum density to one pole or bipolar rectangle or sine pulse with passing through; Can obtain the biological healing process that can be applicable to soft tissue and sclerous tissues in people, the animal and plant more effectively and bigger effect; Thereby cause the acceleration of wound repair, this one pole or bipolar rectangle or sine pulse induction are at every centimetre 10
-6And the peak value electric field between 10 volts (V/cm), and satisfy detectability requirement according to SNR or Power SNR.
The present invention relates to the mechanisms known of wound repair, it relates to the periodic naturally release that is applied to somatomedin suitable in each stage of people, animal and plant or cytokine in wound repair.Especially, wound repair comprises that inflammatory phase, angiogenesis, cell proliferation, collagen produce and the reconstruction phase.There is the timing of specific cytokine and somatomedin to discharge in each stage.Electromagnetic field can strengthen blood flow and strengthen ions bind, and this can quicken each healing stage conversely.Special purpose of the present invention provides improved device and repairs with the effect and the acceleration that strengthen exogenous factor.Use a favourable result of the present invention to be, but because blood flow strengthen or CBAC strengthens thereby accelerate wound repair.The method that the purpose of this invention is to provide improvement to be promoting Expected Results, or improves the relevant cytokine of each stage of wound repair and effect and other effect of somatomedin.
Another object of the present invention is to cause and quicken the healing of chronic wounds, like the non-healing property wound of diabetic ulcer, venous stasis ulcers, pressure ulcer and any cause.
Another object of the present invention is; Through high spectrum density voltage envelope being applied as adjusting or the impulse train defined parameters that requires according to SNR and Power SNR, can be starkly lower than the power requirement than short burst of pulse to the power requirement of the impulse train of such increase persistent period with same frequency range; This comes from the more effective coupling of frequency component and relevant cellular/molecular process.Therefore, obtained the advantage of the power requirement of enhanced dosimetry that is transferred to relevant dielectric pathways and reduction.
Therefore, exist the equipment that more effectively quickens the wound repair in people, animal and plant cell, organ, tissue and the molecule and the needs of method.
Summary of the invention
The use of most of low frequency EMF combines with the application of bone repair and healing.Like this, the current orthopedic clinical use of EMF waveform and EMF waveform comprises relative low frequency component and very low power is arranged, and causes the maximum field in every centimetre one microvolt (mv/cm) scope at the frequency place that is lower than 5KHz.The linear physico-chemical process of scope that uses the electrochemistry model of cell membrane to predict can to expect the EMF waveform patterns of biological effect is to be the basis that is assumed to be of possible EMF target with cell membrane (particularly be combined in the cell membrane or on ion).Therefore, must confirm the scope of waveform parameter, for this waveform parameter, induction field can be for example through using the kinetics that relies on voltage electrochemically to be coupled at cell surface.The expansion of this linear model comprises Lorentz (Lorentz) power Consideration, and its magnetic component that has finally confirmed EMF can play an important role in the EMF treatment.This causes in very low frequency range from the AC of merging and the ion cyclotron resonance and the quantum model of DC magnetic field effect prediction interests.
Continuous sinusoidal wave pulse radiation frequency (PRF) signal that produces by the 27.12MHz that is used for the deep tissues healing is known in the prior art field of diathermy.The follow-up thing of the pulse of diathermy signal is delivered to can in the treatment of infectious disease, exciting the electromagnetic field of non-thermal biological effect at first.Subsequently, reported PFR treatment application, be used for reducing after the wound and the edema of postoperative pain and soft tissue, wound healing, burn treatment and neuranagenesis.The application of PRF of traumatic edema of being used to disappear is used in recent years more and more.In animal and clinical research, use the result of PRF to show so far, edema can moderately be reduced owing to such electromagnetic stimulation.
The present invention is based on biophysics and zooscopy, it exchanges effect to organizational structure sensitivity owing to induced voltage and correlated current with cell and cell.Whether the EMF signal that the mathematical analysis of at least one in use signal to noise ratio (snr) and the PSNR power signal-to-noise ratio (Power SNR), estimation are applied to target pathway structure (like cell, tissue, organ and molecule) is detectable on the thermal noise of ions bind position appearance.The dielectric characteristic of organizational structure is not considered in the EMF dosimetry of prior art, and on the contrary, prior art is utilized the characteristic of isolated cells.Through utilizing dielectric characteristic, the SNR that estimates in the target pathway structure through optimization can strengthen with the activity coupling of the electromagnetic waveforms that the Power SNR mathematical value disposes: at the reparation of people, animal and plant cell, organ, tissue and intramolecular various wounds (for example behind the surgical operation and the wound healing of wound), angiogenesis; The hemoperfusion that improves, vasodilation, vasoconstriction; Decrease in edema, enhanced neovascularization, bone repair; Tendon is repaired; Ligament repair, neomorph, and pain relief.Wound repair enhancement results comes from the blood flow of increase and adjusting and other enhanced biological effect process of angiogenesis and neovascularization.
Noinvasive PRF utilizes the sinusoidal wave impulse train of 27.12MHz in the nearest clinical use of radio frequency, the general width of showing 65 microseconds of each impulse train, and nearly 1700 sinusoidal period of every impulse train, and have different pulse crowd repetitive rate.
Broad spectral density bursts with electromagnetic waveforms of the frequency in the scope of one to 100 megahertz (MHz) is selectively used for people, animal and plant cell, organ, tissue and molecule; Every impulse train has 1 to 100000 pulse, and burst repetition rate is 0.01 to 10000 hertz (Hz).The voltage amplitude envelope of each impulse train be at random, the function of irregular or other similar variable effect, be used in pulse burst envelope, providing broad-spectrum density.Through the mathematical function of the signal of consideration in specific target pathway structure, come defined variable with thermal noise ratio and Power SNR.Waveform Design becomes to regulate living cells growth, state and reparation.The application-specific of these signals includes but not limited to: strengthen the treatment of organ, muscle, joint, skin and hair, behind the surgical operation with the wound healing of wound, angiogenesis, the hemoperfusion of improvement; Vasodilation, vasoconstriction, decrease in edema; Enhanced neovascularization, bone repair, tendon reparation; Ligament repair, neomorph, and pain relief.The application of electromagnetic waveforms can be used for strengthening the healing of various wounds.
According to embodiment of the present invention, the pulse burst envelope of higher spectral density can more effectively be coupled to the dielectric pathways that the physiology is correlated with, for example cell-membrane receptor, change with bonded ion of cellular enzymes and general transmembrane potential.Increased the quantity of the frequency component that is transferred to relevant cellular pathways according to embodiment of the present invention; The biophysics phenomenon in a big way that causes can be applicable to known healing mechanism becomes and can realize, comprises enhanced enzymatic activity, growth factor release and release of cytokines.Through increasing the impulse train persistent period; Use at random or the pulse burst envelope of the envelope of other high spectrum density to one pole or bipolar rectangle or sine pulse with passing through; Can obtain the biological healing process that can be applicable to soft tissue and sclerous tissues in people, the animal and plant more effectively and bigger effect; Thereby cause the acceleration of wound repair, this one pole or bipolar rectangle or sine pulse induction are at every centimetre 10
-6And the peak value electric field between 10 volts (V/cm), and satisfy detectability requirement according to SNR or Power SNR.
The present invention relates to the mechanisms known of wound repair, it relates to the periodic naturally release of somatomedin suitable in each stage of the wound repair that is applied to people, animal and plant or cytokine.Especially, wound repair comprises that inflammatory phase, angiogenesis, cell proliferation, collagen produce and the reconstruction phase.There is the timing of specific cytokine and somatomedin to discharge in each stage.Electromagnetic field can strengthen blood flow and strengthen ions bind, and this can quicken each healing stage conversely.Special purpose of the present invention provides improved device and repairs with the effect and the acceleration that strengthen exogenous factor.Use a favourable result of the present invention to be, but because blood flow strengthen or CBAC strengthens thereby accelerate wound repair.The method that the purpose of this invention is to provide improvement to be promoting the Expected Results of each stage relevant cell factor of wound repair and somatomedin, or improves the cytokine that each stage of wound repair is correlated with and effect and other effect of somatomedin.
Another object of the present invention is to impel and quicken the healing of chronic wounds, like the non-healing property wound of diabetic ulcer, venous stasis ulcers, pressure ulcer and any cause.
Another object of the present invention is; Through high spectrum density voltage envelope being applied as adjusting or the impulse train defined parameters that requires according to SNR and Power SNR, can be starkly lower than the power requirement than short burst of pulse to the power requirement of the impulse train of such increase persistent period with same frequency range; This comes from the more effective coupling of frequency component and relevant cellular/molecular process.Therefore, obtained the advantage of the power requirement of enhanced dosimetry that is transferred to relevant dielectric pathways and reduction.
Therefore, exist the equipment that more effectively quickens the wound repair in people, animal and plant cell, organ, tissue and the molecule and the needs of method.
The specific embodiment
To pulse burst envelope higher spectrum density is provided according to embodiment of the present invention, has caused the enhanced treatment of cell-membrane receptor for example, the dielectric pathways relevant with bonded ion of cellular enzymes and general transmembrane potential variation etc. is renderd a service.Increased the quantity of the frequency component that is transferred to the relevant cell approach according to embodiment of the present invention; Thereby the chance that provides contact to can be applicable in a big way the biophysics phenomenon of known healing mechanism, the for example adjusting of somatomedin and release of cytokines and in the ions bind at adjusting molecule place.According to by at the SNR of transduction in (transduction) approach or the mathematical model of Power SNR definition, through the general at random or other high spectrum density envelope be applied to induction at every centimetre 10
-6And the pulse burst envelope of the one pole of the peak value electric field between 10 volts (V/cm) or bipolar rectangle or sine pulse, can reach bigger effect to the biological agglutination that can be applicable to soft tissue and sclerous tissues.
A favourable outcome of the present invention is; According to mathematical model by SNR in transduction pathway or Power SNR definition; Through using high spectrum density voltage envelope, can be starkly lower than the power requirement of the unmodulated impulse train that is included in the pulse in the identical frequency range to the power requirement of such amplitude adjusted impulse train as regulating or the impulse train defined parameters.Therefore, obtained the advantage of the power requirement of enhanced dosimetry that is transferred to relevant dielectric target approach and reduction.Another advantage of the present invention is an accelerate wound repair.
The mechanisms known of wound repair relates to the periodic naturally release of somatomedin suitable in each stage of the wound repair that is applied to people, animal and plant or cytokine.Especially, wound repair comprises that inflammatory phase, angiogenesis, cell proliferation, collagen produce and the reconstruction phase.There is the timing of specific cytokine and somatomedin to discharge in each stage.Electromagnetic field is considered to strengthen blood flow and strengthens ions bind, and this can quicken each healing stage conversely.The purpose of this invention is to provide improved device, with the effect of enhancing each stage relevant cell factor of wound repair and somatomedin, and promote its Expected Results, or improve its effect and other effect.
The electric current that changes from sensitive time of PEMF or PRF equipment for example flows in molecule, cell, tissue and the organ in the target pathway structure, and these electric currents are a kind of stimulations, and cell can react to this stimulation with physiology's meaningful ways with tissue.The electrical characteristics of target pathway structure influence faradic level and distribution.Molecule, cell, tissue and organ all are in the faradic current approach, are in the slot engagement contact like cell.At the ion that can reside in the binding site place on the lip-deep macromole of film or ligand interaction is can be in response to the process of the dependence voltage of induction field (E), for example electrochemistry.Faradic current arrives these positions through ionic medium on every side.The existence of cell in current pathway makes faradic current (J) along with the time (J (t)) decays comparatively fast.This is because from combining and the electrical impedance increase of the cell of the membrane capacitance of other voltage-sensitive membrane process such as film transhipment and time constant.
The equivalent-circuit model of representing different films and charged interface configurations is obtained.For example, at calcium (Ca
2+) in the combination, since induction E, the bonded Ca at the binding site place
2+Concentration change can be in frequency domain describe by impedance expression, as:
It has the form of the equivalent circuit of series resistance-electric capacity.Wherein ω is the angular frequency that is defined as 2 π f, and f is a frequency, i=-1
1/2, Z
b(ω) be combined impedance, and R
IonAnd C
IonBe the electric capacity that equivalence combines resistance and ions bind approach.The value τ of equivalence binding time constant
Ion=R
IonC
IonPass through τ
Ion=R
IonC
Ion=1/k
bRelevant with ions bind rate constant.Therefore, the characteristic time constant of this approach is confirmed by ions bind kinetics.
Induction E from PEMF or PRF signal can make electric current flow into the ions bind approach, and influences the bonded Ca of time per unit
2+Ionic quantity.Its electrical equivalent is to combine capacitor C in equivalence
IonThe change in voltage at two ends, this is by C
IonThe direct measurement of the change in electrical charge that stores.Electric charge and Ca in binding site
2+Ionic surface concentration is in direct ratio, that is, the storage of electric charge is equivalent to ion or the storage of other charged matter on cell surface and joint.The direct driving force credit of impedance bioelectrical measurement and combination rate constant is analysed, and provides to configuration PMF waveform leads to the band with the target pathway structure to mate the time necessary constant value.This considers the desired frequency range of any given induction E waveform, arrives the target impedance with Best Coupling, as be with logical.
With regulating the bonded ion of molecule is common EMF target, for example with the bonded Ca of calmodulin, CaM
2+(CaM).The use of this approach is based on acceleration of tissue repair, the for example reparation of bone healing, wound healing, hair reparation and molecule, cell, tissue and organ, and these reparations relate to the adjusting of repairing interim d/d somatomedin in difference.Somatomedin, for example platelet derived growth factor (PDGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF) are all related in the suitable healing stage.Angiogenesis and neovascularization are also essential with reparation to tissue growth, and can be regulated by PMF.All these factors all have the Ca/CaM dependency.
Utilize the configurable waveform of Ca/CaM approach, for this waveform, induced power is fully greater than the background heat noise power.Under suitable physiological condition, this waveform can have significant biological effect on physiology.
Power SNR model is to the application need of the Ca/CaM Ca at CaM
2+The knowledge of the electrical equivalent of binding kinetics.In the one-level binding kinetics, at the bonded Ca of CaM binding site
2+Concentration over time can be by equivalent binding time constant τ in frequency domain
Ion=R
IonC
IonCharacterization, wherein R
IonAnd C
IonBe the electric capacity that equivalence combines resistance and ions bind approach.τ
IonPass through τ
Ion=R
IonC
Ion=1/k
bWith ions bind rate constant k
bRelevant.k
bPublished value can be used on then in the cellular array model, to estimate SNR through the voltage that relatively causes by the PRF signal and heat fluctuation at the voltage of CaM binding site.Use the digital value of using of PMF response, like V
Max=6.5 * 10
-7Sec
-1, [Ca
2+]=2.5 μ M, K
D=30 μ M, [Ca
2+CaM]=K
D([Ca
2+]+[CaM]), obtain k
b=665sec
-1(τ
Ion=1.5msec).Such τ
IonValue can be used in the equivalent circuit of ions bind, and the Power SNR analysis can be performed for any waveform configuration.
According to embodiment of the present invention, mathematical model, for example mathematical equation and/or a series of mathematical equation, configurable one-tenth absorb and appear at the thermal noise in all processes relevant with voltage, and represent the minimum threshold requirement of setting up enough SNR.For example, the power spectral density that the configurable one-tenth of mathematical model that the minimum threshold of enough SNR requires comprises thermal noise is set up in expression, so the power spectral density S of thermal noise
n(ω) can be expressed as:
S
n(ω)=4kTRe[Z
M(x,ω)]
Z wherein
M(x ω) is the electrical impedance of target pathway structure, and x is the dimension of target pathway structure, and Re representes the real part of impedance of target pathway structure.Z
M(x ω) can be expressed as:
This equation is clearly shown that the electrical impedance of target pathway structure and all promotes noise filtering from the contribution of extracellular fluid bulk resistor (Re), intracellular fluid bulk resistor (Ri) and intermembranous resistance (Rg) that these resistance are electrically connected to the target pathway structure.
Estimate the monodrome of conventional method use root-mean-square (RMS) noise voltage of SNR.This is through getting S on all relevant with complete film reaction or relevant with the bandwidth of target pathway structure frequencies
n(ω)=4kTRe [Z
M(x, ω)] the square root of integration calculate.SNR can be represented by ratio:
Wherein | V
M(ω) | be when the Frequency Transfer that is chosen amplitude peak at each frequency place voltage when the target pathway structure.
Embodiment of the present invention comprise the pulse burst envelope with high spectrum density so that strengthen therapeutic effect to relevant dielectric pathways, as cell-membrane receptor, with the bonded ion of cellular enzymes and transmembrane potential change.Therefore; Be transferred to a lot of frequency components of relevant cellular pathways through increase; The large-scale biophysics phenomenon that can be applicable to known tissue growth mechanism is attainable, the adjusting somatomedin that for example can be applicable to known tissue growth mechanism and release of cytokines and in the ions bind of adjusting molecule.According to embodiment of the present invention, will be at random or other high spectrum density envelope be applied to induction about 10
-8And the one pole of the peak value electric field between about 100 volts of V/cm or the pulse burst envelope of bipolar rectangle or sine pulse, the biological agglutination that can be applicable to soft tissue and sclerous tissues is produced bigger effect.
According to another embodiment of the present invention; Regulate or the impulse train defined parameters through high spectrum density voltage envelope is applied as, can be starkly lower than the not regulating impulse crowd's of the pulse that comprises in the similar frequencies scope power requirement to the power requirement of the impulse train of such amplitude adjusted.This be because, through with irregular, at random the amplitude of being preferably is imposed to otherwise be essentially uniform pulse burst envelope, has produced the substantial minimizing in the intrachain dutycycle of repetitive burst.Therefore, obtained the two-fold advantage of the power requirement of enhanced dosimetry that is transferred to the relevant dielectric approach and reduction.
With reference to figure 1; Wherein Fig. 1 is the flow chart according to the method for embodiment of the present invention, and for the purpose of treating and preventing, this method is used for through being delivered to the target pathway structure by the electromagnetic signal of pulsed; Ion and part like the animal and human come accelerate wound repair.The target pathway structure also can include but not limited to tissue, cell, organ and molecule.
At least one contoured configuration that will have at least one waveform parameter becomes to be coupled to the target pathway structure, like ion and part (step 101).
Said at least one waveform parameter is chosen to maximize in signal to noise ratio and the PSNR power signal-to-noise ratio in the target pathway structure at least one; So that waveform is detectable (step 102) on background activity in the target pathway structure; For example in the voltage and the fluctuation of the elementary heat in the electrical impedance of target pathway structure, this depends on the state of cell and tissue to background activity, promptly; Whether this state is at least a of rest, growth, displacement and response damage, to be created in useful result on the physiology.In order in the target pathway structure, to be detectable; The value of said at least one waveform parameter can be selected through the constant that uses said target pathway structure; Come in estimated snr and the PSNR power signal-to-noise ratio at least one; To compare elementary heat fluctuation by the voltage of said at least one waveform influence in said target pathway structure and voltage in said target pathway structure and electrical impedance; Thus through the band of maximization in said target pathway structure in said signal to noise ratio in logical and the PSNR power signal-to-noise ratio at least one, by means of said at least one waveform, biological effect adjusts in the present said target pathway structure.
The preferred embodiment of the electromagnetic signal that is produced comprises the impulse train of the random waveform with at least one waveform parameter; This waveform parameter comprises the frequency component of a plurality of scopes from about 0.01Hz to about 100MHz, and wherein said a plurality of frequency components satisfy Power SNR model (step 103).For example multiple electromagnetic signal can be by said at least one waveform inductive or generation (step 104) capacitively.Electromagnetic signal also can be non-repeatability.Electromagnetic signal is through the output of the Coupling device (like electrode or induction apparatus) closely placed with the target pathway structure utmost point, and is coupled to the target pathway structure, like ion and part (step 105).This coupling has increased the bonded adjusting of adjusting molecule in blood flow and ion and part and molecule, tissue, cell and the organ, thereby has quickened wound repair.
Fig. 2 illustrates the preferred embodiment according to equipment of the present invention.This equipment be independently, light-duty with portative.Small-sized control circuit 201 is coupled to the end of at least one adapter 202 like metal wire, but but also radio operation of control circuit.Generating equipment is coupled in the opposite end of said at least one adapter, like electric coil 203.Small-sized control circuit 201 constitutes with the mode of applied mathematical model, and this model is used for configure waveforms.The waveform that is disposed must satisfy Power SNR; So that for given and known target pathway structure; Might select to satisfy the waveform parameter of Power SNR, make on the waveform generation physiology useful result (adjusting of biological example effect) and be detectable in the target pathway structure on background activity.According to the preferred embodiments of the invention applied mathematical model; Come induction mM disodium hydrogen phosphate and time dependent electric field in target pathway structure (like ion and part), comprise that arriving about 0.1 of about 100 microsecond rectangular pulses with per second about 0.1 to about 100 pulses multiple about 1 arrives about 100 milliseconds impulse train.The peak amplitude of induction field is between about 1 μ V/cm and about 100mV/cm, according to the 1/f equation variation of change, wherein f=frequency.Be configured to use the waveform according to the preferred embodiments of the invention to can be applicable in the target pathway structure (like ion and part), preferred total irradiation time is 1 minute to 240 minutes every day.Yet can use other irradiation time.Waveform by small-sized control circuit 201 configurations is directed into generating equipment 203 like electric coil through adapter 202.Generating equipment 203 transmission can be used for providing to target pathway structure such as tissue the pulsed magnetic field of treatment.The one section official hour in small-sized control circuit apply pulse magnetic field, and can be by needed (for example a day 10 times) and the repeated application pulsed magnetic field automatically repeatedly used in the given time period.The configurable one-tenth of small-sized control circuit with any time repetitive sequence apply pulse magnetic field is programmable.Can come accelerate wound repair through merging in the positioning equipment 204 (like bed) according to the preferred embodiments of the invention.Pulsed magnetic field is coupled to target pathway structure such as ion and part, on treatment and prevent disease, has reduced inflammation, thereby advantageously reduced pain, quickened the healing in the target site.When electric coil was used as generating equipment 203, according to Faraday's law, the mM disodium hydrogen phosphate of in the target pathway structure, responding to time dependent electric field capable of using provided power to electric coil.Also can use electromagnetic coupled to use the electromagnetic signal that is produced by generating equipment 203, wherein electrode directly contacts with the other external electric conducting border of skin or target pathway structure.In addition, in another embodiment according to the present invention, also can use Electrostatic Coupling to use the electromagnetic signal that produces by generating equipment 203, wherein between generating equipment 203 is like electrode and target pathway structure such as ion and part, have the air gap.Advantage according to the preferred embodiments of the invention is that its microlight-type coil and miniaturized circuit allow to be used for the General Physics Therapeutic Method, and are used for the place of any desired growth, pain relief and tissue and organ healing.Favourable outcome according to the application of the preferred embodiments of the invention is, tissue growth, reparation and maintenance can be anywhere and accomplished at any time and strengthen, for example when driving or seeing TV.The another favourable outcome of the application of preferred embodiment is, the growth of molecule, cell, tissue and organ, reparation and maintenance can be anywhere and accomplished at any time and strengthen, for example when driving or seeing TV.
Fig. 3 has described the structure chart according to the small-sized control circuit 300 of the preferred embodiments of the invention.Small-sized control circuit 300 produces the waveform that drives generating equipment (like the top wire coil of in Fig. 2, describing).Small-sized control circuit can be triggered by any flip flop equipment (like on/off switch).Small-sized control circuit 300 has power supply such as lithium battery 301.The preferred embodiment of power supply has 3.3 volts output voltage, but also can use other voltage.In another embodiment according to the present invention, power supply can be for example current and power supply socket of external power source, as be coupled to AC/DC supply socket of the present invention through plug and electric wire.Switching Power Supply 302 controls to the voltage of microcontroller 303.The preferred embodiment of microcontroller 303 is used the microcontroller of 8 bit 4MHz, but can use the combination microcontroller of other bit MHz.Switching Power Supply 302 also can convey electrical current to reservior capacitor 304.The preferred embodiments of the invention are used the reservior capacitor with 220 μ F output, but can use other output.Reservior capacitor 304 allows high-frequency impulse to be transported to Coupling device such as induction apparatus (not shown).Microcontroller 303 also control impuls forms device 305 and impulse phase timing controlled 306.Pulse shaper 305 is confirmed pulse shape, burst width, pulse burst envelope shape and burst repetition rate with impulse phase timing controlled 306.The integrated waveform generator like the generator of sine wave or any amount, also can be merged so that specific waveform to be provided.307 controls of voltage level conversion electronic circuit are delivered to the induction field of target pathway structure.Switch Hexfet 308 allows the impulse train of pulses of randomized amplitude to be passed to the output 309 that waveform is sent at least one Coupling device such as induction apparatus.Total irradiation time that microcontroller 303 is gone back the seance of may command target pathway structure such as molecule, cell, tissue and organ.Small-sized control circuit 300 can be configured to programmable and the one section official hour in apply pulse magnetic field, and can be configured to by needed repeatedly application (for example a day 10 times) in the given time period repeated application pulsed magnetic field automatically.Use about 10 minutes to about 30 minutes treatment time according to the preferred embodiments of the invention.
With reference to figure 4A and Fig. 4 B, it illustrates Coupling device 400 according to the preferred embodiments of the invention like induction apparatus.Coupling device 400 can be the electric coil 401 that twines with sub-thread or multiply flexible wire 402, yet also can use solid wire.In according to the preferred embodiments of the invention, metal wire is made of copper, but also can use other material.Multiply flexible magnetic wire 402 makes electric coil 401 can meet specific anatomical structure, like human or animal's the limb wing or joint.The preferred embodiment of electric coil 401 comprise the about 0.01mm of diameter to about 0.1mm about 1 in the sub-thread magnetic metal wire of about 1000 circles and the multiply magnetic metal wire at least one; Metal wire is wrapped in outer dia on the structure that is initially circle between about 2.5cm and the about 50cm, but also can use the circle and the wire diameter of other quantity.The preferred embodiment of electric coil 401 can be used nontoxic PVC mold 403 parcels, but also can use other non-toxic moulds.Electric coil also can be incorporated in dressing, binder, clothes and generally be used for other structure of Wound healing and bone regeneration.
With reference to figure 5, it illustrates the waveform 500 according to embodiment of the present invention.Pulse 501 repeats in the impulse train with finite duration 502.Such persistent period 503 makes the dutycycle of the ratio that can be defined as impulse train persistent period and signal period about 1 to about 10
-5Between.Utilize accurate rectangle 10 microsecond pulses to arrive about 50 milliseconds according to the preferred embodiments of the invention as the pulse 501 about 10 that is used in the impulse train 502; Impulse train 502 has the 1/f amplitude envelops 504 of change; And have, but can use other waveform, envelope and the impulse train cycle of following mathematical model such as SNR and Power SNR corresponding to about 0.1 the finite duration 503 in impulse train cycle between about 10 seconds.
Fig. 6 illustrates the positioning equipment according to the preferred embodiments of the invention, like wrist support.Positioning equipment 600 is worn on people's the wrist 602 like wrist support 601.Positioning equipment can be configured to portative, can be configured to disposablely, maybe can be configured to implantable.Positioning equipment can be used in combination with the present invention in many ways; For example; Through like Velcro
the present invention being sewed up, append on the positioning equipment and the present invention is integrated with in the positioning equipment, and the present invention is kept in place through positioning equipment is configured to elasticity.
In another embodiment according to the present invention, the present invention can be configured to have or do not have the stand-alone device of the virtually any size of positioning equipment, to be used in Anywhere, for example is in, in the clinic, in therapeutic community or
outdoor.Wrist support 601 can be used the for example neoprene manufacturing of any dissection and
support material.Coil 603 is integrated with in the
wrist support 601, makes the signal (waveform of for example in Fig. 5, describing) of the configuration according to the present invention be applied to the sole of the foot portion of wrist bottom from the back at wrist top.Use ruggedized equipment such as Velcro
(not shown) microcircuit to be attached to the outside of wrist support 601.Microcircuit is coupled to an end of at least one connection device such as flexible wire 605.The other end of said at least one connection device is coupled to coil 603.Positioning equipment according to other embodiments of the present invention comprises knee joint, elbow, lower back, shoulder, other dissection wrappage and medicated clothing, for example clothes, fashion accessory and footgear.
With reference to figure 7, it illustrates the electromagnetic therapy equipment of integrating with mattress cushion 700 according to embodiment of the present invention.Also can use mattress.Some lightweight flexible coils 701 are integrated with mattress cushion.Lightweight flexible coils 701 can be made up of fine and soft property conductive metal wire, conductive filament and any other flexible conducting material.Flexible coil is connected at least one end of at least one metal wire 702.Yet the also configurable one-tenth of flexible coil is directly connected to circuit 703 or wireless connections.Be connected to the other end at least of said at least one metal wire according to the light-duty miniaturized circuit 703 of embodiment of the present invention configure waveforms.When triggering light-duty miniaturized circuit 703, configuration is directed into the waveform of flexible coil (701), is coupled to the PEMF signal of target pathway structure with generation.
With reference to figure 8, it illustrates the electromagnetic curing inductive devices of integrating with corset such as medicated bra according to embodiment of the present invention.Some lightweight flexible coils 801 are integrated with medicated bra.Lightweight flexible coils can be made up of fine and soft property conductive metal wire, conductive filament and any other flexible conducting material.Flexible coil is connected at least one end of at least one metal wire 802.Yet the also configurable one-tenth of flexible coil is directly connected to circuit 803 or wireless connections.Be connected to the other end at least of said at least one metal wire according to the light-duty miniaturized circuit 803 of embodiment of the present invention configure waveforms.When being triggered, light-duty miniaturized circuit 803 configure waveforms, this waveform is directed into flexible coil (801), is coupled to the PEMF signal of target pathway structure with generation.
Example 1
Embodiment according to the EMF of being used for signal configures of the present invention is used for the Ca-dependent myosin phosphorylation that standard enzyme is analyzed.Known this enzymatic pathway can strengthen the effectiveness that medicament, chemical agent, enamel and topical agents are applied to people, animal and plant cell, organ, tissue and molecule.For the phosphorylation rate is linear in the time of a few minutes and is sub-saturated Ca
2+Concentration is come choice reaction mixture.In the time of in occurring in damage, or since use be applied on people, animal and plant cell, organ, tissue and the molecule, on or among medicament, chemical agent, enamel and topical agents, this be the Ca to the EMF sensitivity
2+/ CaM has opened biological window.Use experimentizes from isolating myosin light chain of turkey gizzard (MLC) and MLCK (MLCK).Reactant mixture mainly is made up of following material: comprise 40mM Hepes buffer solution, pH and be 7.0 basic solution; 0.5mM ammonium acetate; The 1mg/ml bovine serum albumin, 0.1% (w/v) tween (Tween) 80; And 1mM EGTA.Free Ca
2+In 1-7 μ M scope, change.In case set up Ca
2+Buffering, freshly prepared 70nM CaM, 160nM MLC and 2nM MLCK are added to basic solution, to form final reactant mixture.
Reactant mixture fresh every day to be being used for each serial experiment, and is divided into part and the 1.5ml Eppendorf that packs into the pipe of 100 μ L.All Eppendorf pipes that comprise reactant mixture are maintained at 0 ℃, are transferred to specially designed bain-marie then, and bain-marie is maintained 37 ± 0.1 ℃ through passing FisherScientific model 900 heat exchangers by the lasting perfusion of the water of preheating.Use is immersed in a thermistor detector (like Cole-Parmer model 8110-20) in the Eppendorf pipe at all experimental sessions and comes monitoring temperature.Reaction starts with 2.5 μ M 32P ATP, and stops with the Laemmli sample buffer solution that comprises 30 μ M EDTA.The minima of counting five blank (blank) sample in each experiment.Blank comprises and deducts active component Ca
2+, one of CaM, MLC or MLCK whole analysis of mixtures.Blank counts surpasses the experiment of 300cpm and is abandoned.Phosphorylation was allowed to carry out 5 minutes, and through using TM analytical model 5303 Mark V liquid scintillation counters to being integrated among the MLC
32P counts and estimates phosphorylation.
Signal comprises the repetitive burst of high frequency waveforms.Amplitude maintains constant at 0.2G, and is 1 burst/sec to all irradiation repetitive rate.According to the estimation of explanation when the mathematical analysis of the present invention of time acquisition best power SNR near 500 μ sec of impulse train persistent period, the impulse train persistent period changes to 1000 μ sec from 65 μ sec.The result is presented among Fig. 9, is that the burst width 901 of unit is indicated on the x axle with μ sec wherein, and myosin phosphorylation 902 is indicated on the y axle as treatment/contrasts (treated/sham).Can see that PMF is to Ca
2+With the bonded effect of CaM when the about 500 μ sec near its maximum, just shown in Power SNR model.
These results confirm; For the impulse train persistent period of the best power SNR that is enough to obtain given magnetic field amplitude, will increase the wound repair in people, animal and plant cell, organ, tissue and the molecule to greatest extent according to the EFM signal of embodiment of the present invention configuration.
Example 2
According to embodiment of the present invention, further confirm the use of Power SNR model in vivo in the wound repair model.The Mus wound model is fully characterization on biomechanics and biochemistry, and is used in this research.Utilize weight to surpass health, the young male Sprague Dawley Mus of 300 grams.
Intraperitoneal injection amount with the MPU-295 (Medetomidine) of the ketamine (Ketamine) of 75mg/kg and 0.5mg/kg is come anesthetized animal.After reaching enough anesthesia, pruned in the back, handles with betadin (betadine)/alcoholic solution of dilution, and use aseptic technique to cover the sterilization valance.Use No. 10 dissecting knife, pass skin at the back of each Mus and carry out the 8cm linear incision down to fascia.Edge of wound to break off any remaining skin fiber, is stayed the open wound that diameter is approximately 4cm by the passivity cutting.Obtain hemostasis with institute's applied pressure, to avoid any infringement to skin edge.Use 4-0 acetylene continous suture skin suture edge then.After the operation, animal is accepted the Lepetan of 0.1-0.5mg/kg in peritoneal cavity.They are placed in individual cages, and arbitrarily accept food and water.
The EMF irradiation comprises two pulse radio-frequency waveforms.First is a standard clinical PRF signal, and it comprises the 65 sinusoidal wave μ sec impulse trains of 27.12MHz of 1 Gauss amplitude, and repeats with 600 impulse trains/sec.Second is the PRF signal that reconfigures according to embodiment of the present invention.For this signal, the impulse train persistent period is increased to 2000 μ sec, and amplitude and repetitive rate reduce to 0.2G and 5 impulse trains/sec respectively.Every day, twice Using P RF was 30 minutes.
After debridement, measure tensile strength immediately.The wide strips of two 1cm perpendicular to from the cicatrix of each sample by crosscut, and be used to measure with kg/mm
2Tensile strength for unit.Said strips is cut the same area from every Mus, with the concordance of guaranteeing to measure.Then strips is installed on the tonometer.With the said strips of 10mm/min load, and the maximum, force that produces before the record wound pulled apart.Through to from two strips of same wound with mm
2/ kilogram is averaged for the maximum load of unit, confirms to be used for the final tensile strength of comparison.
The result shows, with respect to 13.0 ± 3.5kg/mm of matched group
2, the average tensile strength of 65 μ sec1 Gauss PRF signals of irradiation group is 19.3 ± 4.3kg/mm
2(P<.01), increased by 48%.On the contrary, with respect to 13.7 ± 4.1kg/mm of matched group
2, for the treatment group, using Power SNR model is 21.2 ± 5.6kg/mm according to the average tensile strength of 2000 μ sec0.2 Gauss PRF signals of embodiment of the present invention configuration
2(P<.01), increased by 54%.The result of these two signals does not have significant difference each other.
The non-thermal pulsed magnetic fields of noinvasive is to be used to cure disunion property fracture, to ease the pain and the edema and the therapy of curing the success of chronic wounds.Two radio frequency EMF devices that are used for this research are being different aspect impulse train persistent period, envelope, amplitude and the repetitive rate.The result that the result that second radio frequency produces and first radio frequency produce has shown the effectiveness according to EMF signal configures of the present invention much at one.
This result follows the pattern of in clinical and basic EMF research, observing.Use correct dosimetry, that is, signal is detectable in the EMF sensitive pathway, the degree of the state decision effect of target.Therefore, normal on every side skeleton does not respond with significant mode on the physiology, though its accept with fracture site in the identical EMF dosage of cell/tissue.Same phenomenon occurs for cells in culture, wherein reported the dependency of EC of state and the ion/ligand of cell cycle, tissue repair.Therefore in fact EMF does not have effect in later stages of wound repair.Through comparing, can infer that the wound of EMF treatment arrives wound repair latter stage than the fast about 1.5 times of ground of matched group with the known organism mechanics of this pattern healing curve.
At cellular level, EMF is shown as and improves TGF-β generation.The EMF type that is used for bone repair has significantly increased external endotheliocyte socket and propagation and fibroblast growth factor β-2.In addition, the anti-CD3 at EMF signal scalable lymphocyte receptor place combines, and shows that EMF can reduce inflammatory reaction.When the EMF effect appears in this skin wound pattern because reduced the time of inflammatory phase and with after-acceleration the collagen generation, realized the healing of quickening.The generation of having reported somatomedin is that Ca/CaM (calmodulin, CaM) is dependent, and has shown that the EMF signal promotes Ca
2+With combining of calmodulin, CaM.In tissue level, demonstrate electric field by the EMF induction of signal of being utilized and comprise the suitable frequency spectrum that will detect in Ca/CaM combination approach.Confirm that also the coupled EMF bone healing of Irritability signal can be increased in external osteoblastic proliferation through directly regulating Ca/CaM.
These results show that the EMF signal that embodiment of the present invention allow to be configured can use obviously lower power to produce.PRF signal according to embodiment of the present invention configuration has quickened the wound repair in the mouse model with the low mode of the clinical EMF signal of power ratio, said clinical EMF signal accelerate wound repair, but need produce more than more power of two one magnitude.
Example 3
This research confirms: the effect according to the electromagnetic field of embodiment of the present invention configuration has been quickened the tendon reparation in the external model.
Average weight is that the young male Sprague-Dawley Mus of 350g is anaesthetized with the intraperitoneal injection of ketamine/MPU-295 mixture of 75mg/kg 0.5mg/kg.Rupture of Achilles tendon is also repaired.Use sterile surgical technique, on right heel string, implement the 2cm center line and vertically cut, simultaneously through making right crus of diaphragm crooked and it is stretching.The blunt cutting is used for using dissecting knife at middle crosscut tendon then tendon and separate tissue on every side.Then use improved Kessler sewing to repair heel string at once with the 6-0 NS.Plantaris muscle tendon is separated but is not repaired.5-0 Ethilon suture skin suture on the tendon of being repaired that use is interrupted.Heel string is not fixed.After the operation, the animals received ketoprofen is with pain management.
At postoperative first day, all animals were randomized to either four treatment groups, 10 animals were arranged in every group.Randomization is followed parallel group protocol, and each animal is randomized to either a treatment group, has ten up to every group.Animal is retained in its specified group.Three matched groups of accepting an active groups and the identical treatment of two particular treatment phases of 30 minutes in during 3 week every day are arranged.The EMF that is used for this research is the pulse radio-frequency waveforms that comprises the repetitive burst of the 27.12MHz sine wave that is sent by the PMF power coil.Use two kinds of configurations.Distribute to group first kind of impulse train persistent period that comprises 65 μ sec of 1, repeat, and be 1 Gauss (G) in the amplitude of tendon target with the speed of 600 impulse trains/sec.Distribute to the impulse train persistent period that group second kind of PRF waveform of 2 comprises 2000 μ sec, repeat with the speed of 5 impulse trains/sec, and be 0.05G in the amplitude of tendon target, the impulse train of distributing to group 3 has the amplitude of 0.1G.There is not signal to be assigned to the control animal of group 4.
Use the monocycle coil to transmit signal, this monocycle coil is mounted to and makes standard plastic mouse cage of removing all metal section and parts as for wherein.This coil is positioned in the 3.5 inches places, top at the bottom of the cage, and parallel with it.With five animals of freely sauntering of each coil treatment.The EMF signal amplitude is examined.Signal amplitude in the Mus treatment cage in the normal range of Mus motion is ± 10% by unification.The concordance of jede Woche validation signal.Each has two cages matched group and active groups, and each cage has its EMF irradiation system of coding separately.Carry out the EMF treatment twice of 30 minute phase every day, up to sacrifice.Control animal is treated being equipped with in the identical cage of identical coil.
When the treatment phase in 3 week finishes, through cutting off at near-end ankle joint is broken away from from the belly of muscle of tendon and at far-end, obtain heel string, keep calcaneus to be connected with foot.Soft tissue that all are outside and sclerous tissues all remove from calcaneus-heel string assembly.After obtaining heel string, carry out the tensile strength test immediately.Than the heel string of vertical orientation, the tendon that is connected with the heel bone is fixed between two metal clips, goes up proximate dorsiflexion of foot so that keep the physiology.Draw back tendon with the constant speed of 0.45mm/sec then, up to fracture, and record peak value tensile strength.All analyzable tendons are in initial crosscut place fracture.Can obtain being used for analyzing from the tensile strength of totally 38 tendons.
After the tendon crosscut 3 week more every group average tensile strength, and analytical data.Tensile strength is calculated as the maximum fracture strength of kilogram/cross-sectional area (is unit with the square centimeter).Than the 80.6 ± 16.6kg/cm that organizes matched group in 4
2, the tendon with the treatment of 65 μ sec signals in group 1 has 99.4 ± 14.6kg/cm
2Average fracture strength.This expression is with respect to 24% increase at 21 days matched group, and this is not significant (p=.055) on statistics.80.6 ± 16.6kg/cm with respect to matched group
2, have obviously higher respectively for 129.4 ± 27.8 kg/cm of 0.05G and 0.1G signal with the tendon from group 2 and group 3 of 2000 μ sec signals treatments
2With 136.4 ± 31.6kg/cm
2Average fracture strength.Than matched group, when the treatment in 3 week finished, group 2 improved 60% and 69% respectively with the mean intensity of group 3.This intensity be increased on the statistics be significant (p<.001), however group 2 and the difference of organizing the average tensile strength between 3 are not significant (p=.541) on statistics.Though statistically significant (the p<.05) of group 1 (65 μ sec impulse train) and the difference of organizing the average tensile strength between 2 (the 2000 μ sec impulse trains).
Here the result who occurs shows, with respect to 21 days contrast tendon after crosscut, the noinvasive pulse electromagnetic field can produce Mus rupture of Achilles tendon intensity up to 69% increase.Be used for all signal accelerated tendon repair of this research, obtain maximum promotion but be to use according to the waveform that relates to the bonded Transduction Mechanism configuration of Ca2+.
Being similar to the mode of skeleton and wound repair, the tendon reparation of stndon sheath and synovial membrane sheath tendon is begun with inflammatory phase, this inflammatory phase is usually directed to the infiltration of inflammatory cell (like macrophage, neutrophil cell and T lymphocyte).Then be that angiogenesis, fibroblast proliferation and the collagen that is mainly the III type produce.At last, cell and collagen fibrils orient are to obtain maximum mechanical strength.These stages all appear in skeleton and the wound repair, and wherein EMF has confirmed effect, and are particularly interim at inflammation, angiogenesis and cell proliferation.
The EMF transduction pathway relates to the ions bind in comprising the adjusting approach of growth factor release.Much depend on the Ca/CaM calmodulin, CaM with tissue growth and relevant somatomedin and the production of cytokines of reparation.EMF is shown as and promotes Ca
2+With combining of calmodulin, CaM.0.05 and the 0.1G signal that use this research of Ca/CaM transduction pathway configuration to use.Purpose is at Ca
2+Produce enough electric field amplitude in the bonded frequency response, that is, and dosage.This will cause lower power, more efficient signal.This model validation, the impulse train persistent period of the amplitude place microsecond scope in the 0.05G scope is satisfied these purposes.Increase the 0.1G signal and do not limit induced current pathway, and reduce the dosage of expection with the small size of guaranteeing Mus tendon target.
EMF promotes bone repair through quickening to return to complete fracture strength.The contrast fracture finally reaches identical biomechanical end point, but sickness rate has increased.Biomechanical acceleration in the Mus linear full-thickness cutaneous wound is observed.It is about 60% that EMF has quickened wound repair in 21 days, obtains complete fracture strength than fast about 50% ground of untreated wound.
Described and be used to strengthen the equipment of pharmaceutical efficacy and the embodiment of method, noted, those skilled in the art can make amendment and change according to top instruction.Therefore, should be understood that in the scope of the present invention and spirit that the change in disclosed particular of the present invention, carried out is being defined by the following claims.